Application of Metal-Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates

✍ Scribed by Sander S. van Berkel; A. (Ton) J. Dirks; Silvie A. Meeuwissen; Dennis L. L. Pingen; Otto C. Boerman; Peter Laverman; Floris L. van Delft; Jeroen J. L. M. Cornelissen; Floris P. J. T. Rutjes

• Book ID: 102788744
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 501 KB
• Volume: 9
• Category: Article
• ISSN: 1439-4227
• DOI: 10.1002/cbic.200800074

✦ Synopsis

Abstract

The tandem 1,3‐dipolar cycloaddition‐retro‐Diels–Alder (tandem crDA) reaction is presented as a versatile method for metal‐free chemoselective conjugation of a DTPA radiolabel to N‐δ‐azido‐cyclo(‐Arg‐Gly‐Asp‐d‐Phe‐Orn‐) via oxanorbornadiene derivatives. To this end, the behavior of several trifluoromethyl‐substituted oxanorbornadiene derivatives in the 1,3‐dipolar cycloaddition was studied and optimized to give a clean and efficient method for bio‐orthogonal ligation in an aqueous environment. After radioisotope treatment, the resulting ^111^In‐labeled c(RGD)‐CF~3~‐triazole‐DTPA conjugate was subjected to preliminary biological evaluation and showed high affinity for α~v~β~3~ (IC~50~=192 nM) and favorable pharmacokinetics.